Monoclonal antibodies are becoming increasingly important tools for the diagnosis or treatment of diseases or other physical conditions. They also show promise in industrial applications, for example, for the purification of commercially valuable materials found in mixtures difficult to resolve by other than affinity purification.
For these applications, the antibody is selected based upon its ability to bind an antigen. In certain applications the antibody may be used without modification. For example, passive therapeutic treatments use unmodified antibody. Most applications, however, including those with the most current commercial significance, use an antibody that has been modified in some way. Thus, the antibody may be bound to a solid phase and used as an immunoadsorbent in affinity purification or immunometric assays.
In other applications the antibody may be labeled with, for example, a radionuclide for use in detecting antigens in diagnostic assays and for in vivo imaging. An antibody labeled with a radionuclide, drug or toxin can have therapeutic applications.
The ability to label monoclonal antibodies is complicated in that each such antibody, being a discrete chemical compound, exhibits its own labeling idiosyncracies. Therefore, the ability to label efficiently and simply is highly desirable.
In that regard, we have proposed to label monoclonal antibodies with metallic radionuclides by the use of a chelating agent for the metal. The chelating agent is first conjugated with the monoclonal antibody of choice. Since the same chelating agent may bind a number of different metals, it is only necessary to work out the chemical protocol for optimal binding of the antibody to the chelating agent in order to be able to label the antibody with any of the several radionuclides which the chelating agent will bind. While this procedure has greatly simplified the labeling of monoclonal antibodies with radionuclides, it is still necessary to determine the optimal binding conditions for each combination of antibody and chelating agent.